Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation.

J Biol Chem

Division of Clinical Laboratory Medicine and Hematology/Oncology, Faculty of Medicine, Tottori University, 86 Nishi-Cho, Yonago 683-8503, Japan; Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku Uchinada, Ishikawa 902-0293, Japan. Electronic address:

Published: October 2011

Transferrin (Tf) endocytosis and recycling are essential for iron uptake and the regulation of cell proliferation. Tf and Tf receptor (TfR) complexes are internalized via clathrin-coated pits composed of a variety of proteins and lipids and pass through early endosomes to recycling endosomes. We investigated the role of sphingomyelin (SM) synthases (SMS1 and SMS2) in clathrin-dependent trafficking of Tf and cell proliferation. We employed SM-deficient lymphoma cells that lacked SMSs and that failed to proliferate in response to Tf. Transfection of SMS1, but not SMS2, enabled these cells to incorporate SM into the plasma membrane, restoring Tf-mediated proliferation. SM-deficient cells showed a significant reduction in clathrin-dependent Tf uptake compared with the parental SM-producing cells. Both SMS1 gene transfection and exogenous short-chain SM treatment increased clathrin-dependent Tf uptake in SM-deficient cells, with the Tf being subsequently sorted to Rab11-positive recycling endosomes. We observed trafficking of the internalized Tf to late/endolysosomal compartments, and this was not dependent on the clathrin pathway in SM-deficient cells. Thus, SMS1-mediated SM synthesis directs Tf-TfR to undergo clathrin-dependent endocytosis and recycling, promoting the proliferation of lymphoma cells.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195583PMC
http://dx.doi.org/10.1074/jbc.M111.228593DOI Listing

Publication Analysis

Top Keywords

cell proliferation
12
sm-deficient cells
12
trafficking cell
8
endocytosis recycling
8
recycling endosomes
8
sms1 sms2
8
lymphoma cells
8
clathrin-dependent uptake
8
cells
7
proliferation
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!